Summary of findings 3. Summary of findings ‐ Inhaled mannitol compared with control (non‐respirable mannitol) for people with cystic fibrosis, hospitalised due to pulmonary exacerbations.

Inhaled mannitol compared with control (non‐respirable mannitol) for people with cystic fibrosis, hospitalised due to pulmonary exacerbations
Patient or population: children and young people with CF Settings: children and young people hospitalised due to pulmonary exacerbations (14 days) and up to 1 month of outpatient follow‐up Intervention: inhaled mannitol Comparison: non‐respirable mannitol
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Non‐respirable mannitol	Inhaled mannitol
HRQoL ‐ change from baseline in CFCS total score and CFQ‐R respiratory domain Follow‐up: up to 1 month	There was no statistically significant difference in the change from baseline in HRQoL (CFCS total score or CFQ‐R respiratory domain) at hospital discharge or at 1 month follow‐up.		NA	22 1 study	⊕⊝⊝⊝ very low1,2,3
Lung function: FEV1 mL% predicted (change from baseline) Follow‐up: NA	Outcome not reported.				NA
Lung function: FEV1 % predicted (change from baseline) Follow‐up: up to 1 month	The mean difference in the change from baseline in FEV1 (% predicted in the mannitol group compared to the control group was 4.60% higher (3.80% lower to 13.00% higher) at hospital discharge and 5.40% higher (2.70% lower to 13.50% higher) after 1‐month follow‐up.		NA	22 1 study	⊕⊕⊝⊝ low1,2
Lung function: FVC % predicted (change from baseline) Follow‐up: up to 1 month	The mean difference in the change from baseline in FVC (% predicted in the mannitol group compared to the control group was 2.80% higher (3.60% lower to 9.20% higher) at hospital discharge and 1.70% higher (4.10% lower to 7.50% higher) after 1‐month follow‐up.		NA	22 1 study	⊕⊕⊝⊝ low1,2
Lung function: FEF25-75 % predicted (change from baseline) Follow‐up: up to 1 month	The mean difference in the change from baseline in FEV1 (% predicted in the mannitol group compared to the control group was 12.80% higher (3.30% lower to 28.90% higher) at hospital discharge and 3.90% higher (‐10.70% lower to 18.50% higher) after 1‐month follow‐up.		NA	22 1 study	⊕⊕⊝⊝ low1,2
Adverse events relating to treatment Follow‐up: up to 1 month	Vomiting (mucous) haemoptysis (flecks only) and blurred vision each occurred in one participant in the control group.	Vomiting (mucous), dizziness and headaches each occurred in one participant in the 400mg mannitol group.	NA	22 1 study	⊕⊕⊝⊝ low1,2	Also stated that no serious adverse events occurred. Severity and relationship to treatment not stated.
*The basis for the assumed risk is the range of mean values in the control group and the corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CF: cystic fibrosis; CFCS: Cystic Fibrosis Clinical Score;CFQ‐R: Cystic Fibrosis Questionnaire‐Revised version, CI: confidence interval; FEF25-75: mid‐expiratory flow; FEV1: forced expiratory volume at one second; FVC: forced vital capacity; HRQoL: health‐related quality of life; NA: not applicable.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

1. Evidence downgraded due to indirectness: the participant population included only those with CF who passed the tolerance test and not all potential participants with CF. The population recruited into the study were hospitalised, so results may not be applicable to all individuals with CF.

2. Evidence downgraded due to imprecision: small sample size and wide confidence intervals around the effect size.

3. Evidence downgraded due to indirectness: the CFQ‐R tool used in the studies was not designed to assess mucolytics. Also, pooling of the age‐appropriate tools may not be valid so results should be interpreted with caution.